Nafees Ud Din

Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review

Background:It is unclear whether more timely cancer diagnosis brings favourable outcomes, with much of the previous evidence, in some cancers, being equivocal. We set out to determine whether there is an association between time to diagnosis, treatment and clinical outcomes, across all cancers for symptomatic presentations.Methods:Systematic review of the literature and narrative synthesis.Results:We included 177 articles reporting 209 studies. These studies varied in study design, the time intervals assessed and the outcomes reported. Study quality was variable, with a small number of higher-quality studies. Heterogeneity precluded definitive findings. The cancers with more reports of an association between shorter times to diagnosis and more favourable outcomes were breast, colorectal, head and neck, testicular and melanoma.Conclusions:This is the first review encompassing many cancer types, and we have demonstrated those cancers in which more evidence of an association between shorter times to diagnosis and more favourable outcomes exists, and where it is lacking. We believe that it is reasonable to assume that efforts to expedite the diagnosis of symptomatic cancer are likely to have benefits for patients in terms of improved survival, earlier-stage diagnosis and improved quality of life, although these benefits vary between cancers.

An evaluation of the effectiveness and cost effectiveness of the National Exercise Referral Scheme in Wales, UK: a randomised controlled trial of a public health policy initiative.

Background The Wales National Exercise Referral Scheme (NERS) is a 16-week programme including motivational interviewing, goal setting and relapse prevention. Method A pragmatic randomised controlled trial with nested economic evaluation of 2160 inactive participants with coronary heart disease risk (CHD, 1559, 72%), mild to moderate depression, anxiety or stress (79, 4%) or both (522, 24%) randomised to receive (1) NERS or (2) normal care and brief written information. Outcome measures at 12 months included the 7-day physical activity recall, the hospital anxiety and depression scale. Results Ordinal regression identified increased physical activity among those randomised to NERS compared with those receiving normal care in all participants (OR 1.19, 95% CI 0.99 to 1.43), and among those referred for CHD only (OR 1.29, 95% CI 1.04 to 1.60). For those referred for mental health reason alone, or in combination with CHD, there were significantly lower levels of anxiety (OR −1.56, 95% CI −2.75 to −0.38) and depression (OR −1.39, 95% CI −2.60 to −0.18), but no effect on physical activity. The base-case incremental cost-effectiveness ratio was £12 111 per quality adjusted life year, falling to £9741 if participants were to contribute £2 per session. Conclusions NERS was effective in increasing physical activity among those referred for CHD risk only. Among mental health referrals, NERS did not influence physical activity but was associated with reduced anxiety and depression. Effects were dependent on adherence. NERS is likely to be cost effective with respect to prevailing payer thresholds. Trial registration Current Controlled Trials ISRCTN47680448.

Comparison of cancer diagnostic intervals before and after implementation of NICE guidelines : analysis of data from the UK General Practice Research Database.

Background:The primary aim was to use routine data to compare cancer diagnostic intervals before and after implementation of the 2005 NICE Referral Guidelines for Suspected Cancer. The secondary aim was to compare change in diagnostic intervals across different categories of presenting symptoms.Methods:Using data from the General Practice Research Database, we analysed patients with one of 15 cancers diagnosed in either 2001–2002 or 2007–2008. Putative symptom lists for each cancer were classified into whether or not they qualified for urgent referral under NICE guidelines. Diagnostic interval (duration from first presented symptom to date of diagnosis in primary care records) was compared between the two cohorts.Results:In total, 37 588 patients had a new diagnosis of cancer and of these 20 535 (54.6%) had a recorded symptom in the year prior to diagnosis and were included in the analysis. The overall mean diagnostic interval fell by 5.4 days (95% CI: 2.4–8.5; P<0.001) between 2001–2002 and 2007–2008. There was evidence of significant reductions for the following cancers: (mean, 95% confidence interval) kidney (20.4 days, −0.5 to 41.5; P=0.05), head and neck (21.2 days, 0.2–41.6; P=0.04), bladder (16.4 days, 6.6–26.5; P⩽0.001), colorectal (9.0 days, 3.2–14.8; P=0.002), oesophageal (13.1 days, 3.0–24.1; P=0.006) and pancreatic (12.6 days, 0.2–24.6; P=0.04). Patients who presented with NICE-qualifying symptoms had shorter diagnostic intervals than those who did not (all cancers in both cohorts). For the 2007–2008 cohort, the cancers with the shortest median diagnostic intervals were breast (26 days) and testicular (44 days); the highest were myeloma (156 days) and lung (112 days). The values for the 90th centiles of the distributions remain very high for some cancers. Tests of interaction provided little evidence of differences in change in mean diagnostic intervals between those who did and did not present with symptoms specifically cited in the NICE Guideline as requiring urgent referral.Conclusion:We suggest that the implementation of the 2005 NICE Guidelines may have contributed to this reduction in diagnostic intervals between 2001–2002 and 2007–2008. There remains considerable scope to achieve more timely cancer diagnosis, with the ultimate aim of improving cancer outcomes.

The clinical effectiveness and cost-effectiveness of management strategies for sciatica: systematic review and economic model.

Background Sciatica is a symptom characterised by well-localised leg pain with a sharp, shooting or burning quality that radiates down the back of the leg and normally to the foot or ankle. It is often associated with numbness or altered sensation in the leg. Objectives To determine the clinical effectiveness and cost-effectiveness of different management strategies for sciatica. Data sources Major electronic databases (e.g. MEDLINE, EMBASE and NHS Economic Evaluation Database) and several internet sites including trial registries were searched up to December 2009. Review methods Systematic reviews were undertaken of the clinical effectiveness and cost-effectiveness of different treatment strategies for sciatica. Effectiveness data were synthesised using both conventional meta-analyses and mixed treatment comparison (MTC) methods. An economic model was then developed to estimate costs per quality-adjusted life-year gained for each treatment strategy. Results The searches identified 33,590 references, of which 270 studies met the inclusion criteria and 12 included a full economic evaluation. A further 42 ongoing studies and 93 publications that could not be translated were identified. The interventions were grouped into 18 treatment categories. A larger number of studies evaluated invasive interventions and non-opioids than other non-invasive interventions. The proportion of good-quality studies for each treatment category ranged from 0% to 50%. Compared with studies of less invasive interventions, studies of invasive treatments were more likely to confirm disc herniation by imaging, to limit patients included to those with acute sciatica (< 3 months’ duration) and to include patients who had received previous treatment. The MTC analyses gave an indication of relative therapeutic effect. The statistically significant odds ratios of global effect compared with inactive control were as follows: disc surgery 2.8, epidural injection 3.1, chemonucleolysis 2.0 and non-opioids 2.6. Disc surgery and epidural injections were associated with more adverse effects than the inactive control. There was some evidence for the effectiveness of biological agents and acupuncture. Opioid medication and activity restriction were found to be less effective than the comparator interventions and opioids were associated with more adverse effects than the inactive control. The full economic evaluations were of reasonable to good quality, but were not able to fully address our research question. Although individual studies raised a number of important issues, it was difficult to draw meaningful conclusions across studies because of their heterogeneity. The economic model demonstrated that stepped-care approaches to patient management were likely to be cost-effective, relative to strategies that involved direct referral to disc surgery. Limitations The limited number of studies for some comparisons, the high level of heterogeneity (within treatment comparisons) and the potential inconsistency (between treatment comparisons) weaken the interpretation of the MTC analyses. Conclusions These findings provide support for the effectiveness of currently used therapies for sciatica such as non-opioid medication, epidural corticosteroid injections and disc surgery, but also for chemonucleolysis, which is no longer used in the UK NHS. These findings do not provide support for the effectiveness of opioid analgesia, which is widely used in this patient group, or activity restriction. They also suggest that less frequently used treatments, such as acupuncture, and experimental treatments, such as anti-inflammatory biological agents, may be effective. Stepped-care approaches to treatment for patients with sciatica are cost-effective relative to direct referral for surgery. Future research should include randomised controlled trials with concurrent economic evaluation of biological agents and acupuncture compared with placebo or with currently used treatments. Development of alternative economic modelling approaches to assess relative cost-effectiveness of treatment regimes, based on the above trial data, would also be beneficial. Funding The National Institute for Health Research Health Technology Assessment programme.

Comparative clinical effectiveness of management strategies for sciatica: systematic review and network meta-analyses

BACKGROUND There are numerous treatment approaches for sciatica. Previous systematic reviews have not compared all these strategies together. PURPOSE To compare the clinical effectiveness of different treatment strategies for sciatica simultaneously. STUDY DESIGN Systematic review and network meta-analysis. METHODS We searched 28 electronic databases and online trial registries, along with bibliographies of previous reviews for comparative studies evaluating any intervention to treat sciatica in adults, with outcome data on global effect or pain intensity. Network meta-analysis methods were used to simultaneously compare all treatment strategies and allow indirect comparisons of treatments between studies. The study was funded by the UK National Institute for Health Research Health Technology Assessment program; there are no potential conflict of interests. RESULTS We identified 122 relevant studies; 90 were randomized controlled trials (RCTs) or quasi-RCTs. Interventions were grouped into 21 treatment strategies. Internal and external validity of included studies was very low. For overall recovery as the outcome, compared with inactive control or conventional care, there was a statistically significant improvement following disc surgery, epidural injections, nonopioid analgesia, manipulation, and acupuncture. Traction, percutaneous discectomy, and exercise therapy were significantly inferior to epidural injections or surgery. For pain as the outcome, epidural injections and biological agents were significantly better than inactive control, but similar findings for disc surgery were not statistically significant. Biological agents were significantly better for pain reduction than bed rest, nonopioids, and opioids. Opioids, education/advice alone, bed rest, and percutaneous discectomy were inferior to most other treatment strategies; although these findings represented large effects, they were statistically equivocal. CONCLUSIONS For the first time, many different treatment strategies for sciatica have been compared in the same systematic review and meta-analysis. This approach has provided new data to assist shared decision-making. The findings support the effectiveness of nonopioid medication, epidural injections, and disc surgery. They also suggest that spinal manipulation, acupuncture, and experimental treatments, such as anti-inflammatory biological agents, may be considered. The findings do not provide support for the effectiveness of opioid analgesia, bed rest, exercise therapy, education/advice (when used alone), percutaneous discectomy, or traction. The issue of how best to estimate the effectiveness of treatment approaches according to their order within a sequential treatment pathway remains an important challenge.

Age and Gender Variations in Cancer Diagnostic Intervals in 15 Cancers: Analysis of Data from the UK Clinical Practice Research Datalink

Background Time from symptomatic presentation to cancer diagnosis (diagnostic interval) is an important, and modifiable, part of the patient’s cancer pathway, and can be affected by various factors such as age, gender and type of presenting symptoms. The aim of this study was to quantify the relationships of diagnostic interval with these variables in 15 cancers diagnosed between 2007 and 2010 using routinely collected data from the Clinical Practice Research Datalink (CPRD) in the UK. Methods Symptom lists for each cancer were prepared from the literature and by consensus amongst the clinician researchers, which were then categorised into either NICE qualifying (NICE) or not (non-NICE) based on NICE Urgent Referral Guidelines for Suspected Cancer criteria. Multivariable linear regression models were fitted to examine the relationship between diagnostic interval (outcome) and the predictors: age, gender and symptom type. Results 18,618 newly diagnosed cancer patients aged ≥40 who had a recorded symptom in the preceding year were included in the analysis. Mean diagnostic interval was greater for older patients in four disease sites (difference in days per 10 year increase in age; 95% CI): bladder (10.3; 5.5 to 15.1; P<0.001), kidney (11.0; 3.4 to 18.6; P=0.004), leukaemia (18.5; 8.8 to 28.1; P<0.001) and lung (10.1; 6.7 to 13.4; P<0.001). There was also evidence of longer diagnostic interval in older patients with colorectal cancer (P<0.001). However, we found that mean diagnostic interval was shorter with increasing age in two cancers: gastric (-5.9; -11.7 to -0.2; P=0.04) and pancreatic (-6.0; -11.2 to -0.7; P=0.03). Diagnostic interval was longer for females in six of the gender non-specific cancers (mean difference in days; 95% CI): bladder (12.2; 0.8 to 23.6; P=0.04), colorectal (10.4; 4.3 to 16.5; P=0.001), gastric (14.3; 1.1 to 27.6; P=0.03), head and neck (31.3; 6.2 to 56.5; P=0.02), lung (8.0; 1.2 to 14.9; P=0.02), and lymphoma (19.2; 3.8 to 34.7; P=0.01). Evidence of longer diagnostic interval was found for patients presenting with non-NICE symptoms in 10 of 15 cancers (mean difference in days; 95% CI): bladder (62.9; 48.7 to 77.2; P<0.001), breast (115.1; 105.9 to 124.3; P<0.001), cervical (60.3; 31.6 to 89.0; P<0.001), colorectal (25.8; 19.6 to 31.9; P<0.001), gastric (24.1; 3.4 to 44.8; P=0.02), kidney (22.1; 4.5 to 39.7; P=0.01), oesophageal (67.0; 42.1 to 92.0; P<0.001), pancreatic (48.6; 28.1 to 69.1; P<0.001), testicular (36.7; 17.0 to 56.4; P< 0.001), and endometrial (73.8; 60.3 to 87.3; P<0.001). Pooled analysis across all cancers demonstrated highly significant evidence of differences overall showing longer diagnostic intervals with increasing age (7.8 days; 6.4 to 9.1; P<0.001); for females (8.9 days; 5.5 to 12.2; P<0.001); and in non-NICE symptoms (27.7 days; 23.9 to 31.5; P<0.001). Conclusions We found age and gender-specific inequalities in time to diagnosis for some but not all cancer sites studied. Whilst these need further explanation, these findings can inform the development and evaluation of interventions intended to achieve timely diagnosis and improved cancer outcomes, such as to provide equity across all age and gender groupings.

Mixed-method process evaluation of the Welsh National Exercise Referral Scheme

Purpose – Primary-care referral to community-based exercise specialists (exercise referral) is common in the UK despite limited evidence of effectiveness. A recent pragmatic randomised trial of the Welsh National Exercise Referral Scheme (NERS), demonstrated promising impacts upon physical activity and mental health. This paper presents a mixed-method process evaluation exploring how outcomes were achieved. Design/methodology/approach – Structured observation, implementer interviews and routine data assessed the extent to which NERS was implemented as intended. Baseline trial data were combined with routine monitoring data for the purposes of profiling uptake and adherence. Semi-structured patient interviews explored processes of change and the emergence of social patterning in responses to the scheme. Findings – NERS offered patients a programme of supervised, group-based discounted exercise. However, motivational interviewing, goal-setting and patient follow-up protocols were delivered poorly. The high degree of professional support was perceived as helping patients to build confidence and assimilate into exercise environments. Patient-only classes provided social contacts, a supportive context and realistic models. Patterning in uptake emerged from access issues, with uptake lower among non-car owners. Adherence was poorer among mental health patients, younger patients and those who were least active prior to referral to NERS. Originality/value – In practice, although the NERS RCT demonstrated positive impacts on physical activity and mental health, process evaluation data indicate that the intervention was not entirely delivered as intended. Mixed-method process evaluation served crucial functions in understanding implementation and functioning, offering insights into the roles of professional support and exercise classes in promoting activity and mental health, and the emergence of social patterning in responses to an ERS.

Health Professionals' Perspectives on Exercise Referral and Physical Activity Promotion in Primary Care: Findings from a Process Evaluation of the National Exercise Referral Scheme in Wales.

Background and objectives: Referring clinicians’ experiences of exercise referral schemes (ERS) can provide valuable insights into their uptake. However, most qualitative studies focus on patient views only. This paper explores health professionals’ perceptions of their role in promoting physical activity and experiences of a National Exercise Referral Scheme (NERS) in Wales. Design: Qualitative semi-structured group interviews. Setting: General practice premises. Methods: Nine semi-structured group interviews involving 46 health professionals were conducted on general practice premises in six local health board areas. Purposive sampling taking into account area deprivation, practice size and referral rates was employed. Interviews were transcribed verbatim and analysed using the Framework method of thematic analysis. Results: Health professionals described physical activity promotion as important, although many thought it was outside of their expertise and remit, and less important than other health promotion activities such as smoking cessation. Professionals linked decisions on whether to advise physical activity to patients to their own physical activity levels and to subjective judgements of patient motivation. While some described ERS as a holistic alternative to medication, with potential social benefits, others expressed concerns regarding their limited reach and potential to exacerbate inequalities. Barriers to referral included geographic isolation and uncertainties about patient selection criteria, medico-legal responsibilities and a lack of feedback about patient progress. Conclusion: Clinicians’ concerns about expertise, priority setting and time constraints should be addressed to enhance physical activity promotion in primary care. Further research is needed to fully understand decision making relating to provision of physical activity advice and use of ERS.

Cost-effectiveness of different strategies to manage patients with sciatica.

Summary A model‐based economic evaluation demonstrates that stepped approaches based on initial treatment with nonopioids are most likely to represent the most cost‐effective regimens for sciatica. ABSTRACT The aim of this paper is to estimate the relative cost‐effectiveness of treatment regimens for managing patients with sciatica. A deterministic model structure was constructed based on information from the findings from a systematic review of clinical effectiveness and cost‐effectiveness, published sources of unit costs, and expert opinion. The assumption was that patients presenting with sciatica would be managed through one of 3 pathways (primary care, stepped approach, immediate referral to surgery). Results were expressed as incremental cost per patient with symptoms successfully resolved. Analysis also included incremental cost per utility gained over a 12‐month period. One‐way sensitivity analyses were used to address uncertainty. The model demonstrated that none of the strategies resulted in 100% success. For initial treatments, the most successful regime in the first pathway was nonopioids, with a probability of success of 0.613. In the second pathway, the most successful strategy was nonopioids, followed by biological agents, followed by epidural/nerve block and disk surgery, with a probability of success of 0.996. Pathway 3 (immediate surgery) was not cost‐effective. Sensitivity analyses identified that the use of the highest cost estimates results in a similar overall picture. While the estimates of cost per quality‐adjusted life year are higher, the economic model demonstrated that stepped approaches based on initial treatment with nonopioids are likely to represent the most cost‐effective regimens for the treatment of sciatica. However, development of alternative economic modelling approaches is required.

Fracture in the Elderly Multidisciplinary Rehabilitation (FEMuR): study protocol for a phase II randomised feasibility study of a multidisciplinary rehabilitation package following hip fracture [ISRCTN22464643]

BackgroundProximal femoral fracture is a common, major health problem in old age resulting in loss of functional independence and a high-cost burden on society, with estimated health and social care costs of £2.3 billion per year in the UK. Rehabilitation has the potential to maximise functional recovery and maintain independent living, but evidence of effectiveness is lacking. Usual rehabilitation care is delivered by a multi-disciplinary team in the hospital and in the community. An ‘enhanced rehabilitation’ intervention has been developed consisting of a workbook, goal-setting diary and extra therapy sessions, designed to improve self-efficacy and increase the amount and quality of the practice of physical exercise and activities of daily living.Methods/designThis paper describes the design of a phase II study comprising an anonymous cohort of all proximal femoral fracture patients admitted to the three acute hospitals in Betsi Cadwaladr University Health Board over a 6-month period with a randomised feasibility study comparing the enhanced rehabilitation intervention with usual care. These will assess the feasibility of a future definitive randomised controlled trial and concurrent economic evaluation in terms of recruitment, retention, outcome measure completion, compliance with the intervention and fidelity of delivery, health service use data, willingness to be randomised and effect size for a future sample size calculation. Focus groups will provide qualitative data to contribute to the assessment of the acceptability of the intervention amongst patients, carers and rehabilitation professionals and the feasibility of delivering the planned intervention. The primary outcome measure is function assessed by the Barthel Index. Secondary outcomes measure the ability to perform activities of daily living, anxiety and depression, potential mediators of outcomes such as hip pain, self-efficacy and fear of falling, health utility, health service use, objectively assessed physical function and adverse events. Participants’ preference for rehabilitation services will be assessed in a discrete choice experiment.DiscussionPhase II studies are an opportunity to not only assess the feasibility of trial methods but also to compare different methods of outcome measurement and novel methods of obtaining health service use data from routinely collected patient information.Trial registrationCurrent Controlled Trials ISRCTN22464643, UKCRN16677.